Nitration of 2-substituted pyrimidine-4,6-diones, structure and reactivity of 5,5-gem-dinitropyrimidine-4,6-diones

Article abstract of DOI:10.1021/jo025952x

Nitration of some 2-substituted pyrimidine-4,6-diones in sulfuric acid was studied, which afforded previously unknown 5,5-gem-dinitropyrimidine-4,6-diones in high yields. The gem-dinitro products were easily attacked by nucleophiles with concomitant formation of gem-dinitroacetyl derivatives, which in turn could be further hydrolyzed to salts of dinitromethane and triureas.

Full text of DOI:10.1021/jo025952x

Nitr a tion of 2-Su bstitu ted P yr im id in e-4,6-d ion es, Str u ctu r e a n d
Rea ctivity of 5,5-gem -Din itr op yr im id in e-4,6-d ion es
Abraham Langlet, Nikolaj V. Latypov,* Ulf Wellmar, Ulf Bemm, and Patrick Goede
FOI, Swedish Defence Research Agency, Department of Energetic Materials, SE-14725 Tumba, Sweden
J an Bergman and Ivan Romero
Department of Organic Chemistry, CNT, NOVUM Research Park, SE-141 57 Huddinge, Sweden
nikolaj.latypov@foi.se
Received May 22, 2002
Nitration of some 2-substituted pyrimidine-4,6-diones in sulfuric acid was studied, which afforded
previously unknown 5,5-gem-dinitropyrimidine-4,6-diones in high yields. The gem-dinitro products
were easily attacked by nucleophiles with concomitant formation of gem-dinitroacetyl derivatives,
which in turn could be further hydrolyzed to salts of dinitromethane and triureas.
In tr od u ction
excluded, but not taken into consideration, since the
reversibility of this reaction11 allows one to expect
complete consumption of nitric acid in the irreversible
formation of C-nitro compounds. The courses of the
reactions were monitored by UV spectroscopy.
There are only a few examples of nitrations at
saturated carbon atoms in aliphatic and heterocyclic
molecules, leading to the formation of gem-dinitro- or
trinitromethyl compounds.1
-5
Some substituted five-
membered azolones have recently been shown to behave
in the same way.6 However, in those cases where gem-
dinitration occurred in the heterocyclic ring it was
accompanied by nitration either in the fused aromatic
Discu ssion
-8
It has long been known that nitration of barbituric acid
(1b) in nitric acid at room temperature gives exclusive
mononitration of the substrate in the 5-position. The
7
12
system or in the exo-cyclic substituent, which made it
difficult to differentiate the sequence of the nitration
steps.
same results were obtained by us when compounds 1a -c
dissolved in concentrated sulfuric acid (85-95%) were
treated with 1 equiv of nitric acid at room temperature.
Quick and quantitative formation of 5-mononitro deriva-
tives 2a -c was observed. Excess of nitric acid in the
nitrating mixture (1-1.5 mol per mol of 2a -c) and a
higher reaction temperature (30-60 °C) caused further
nitration of these compounds. This was first detected by
the appearance of a new absorption maximum (355-365
nm) in the UV spectra of the quenched samples in
addition to the absorption maximum of the mononitrated
products (320-330 nm).
Trying to overcome these difficulties and to see if the
presence of only carbonyl groups could promote gem-
dinitration in nitrogen heterocyles we have studied the
nitration of several pyrimidinones. Nitric acid in sulfuric
acid was chosen as the reaction medium as this had
previously been found to favor the formation of gem-
dinitro compounds.4
-10
2
-Aminopyrimidine-4,6-dione (1a ), barbituric acid (1b),
and its N,N-dimethyl derivative (1c) were studied as
compounds having only one reaction site, namely the
It was not possible to study the kinetics of the second
nitration step because of the strong overlap of the
absorption curves from the mono- and dinitrated prod-
ucts. A rough estimation of reaction times could be
obtained by following the smooth increase of the absorp-
tion at 360 nm. Maximum absorption was usually
reached after a few hours whereupon it remained con-
stant, thus indicating the formation of stable C-nitro
compounds. Compound 1b was completely converted to
the gem-dinitrated product 3b after 4 h at room temper-
ature. 2-Aminopyrimidine-4,6-dione was found, not un-
expectedly, to be more reactive, and consequently full
5
-position in the ring, which might be susceptible to this
type of nitration. The possibility of N-nitration was not
(
1) Nielsen, A. T. Nitrocarbons; VCH: New York, 1995.
(2) Noble, P. J .; Borgardt, F. G.; Reed, W. L. Chem. Rev. 1964, 64,
1
9-57.
(3) Parker, C. O.; Emmons, W. D.; Rolewicz, H. A.; McCallum, K.
S. Tetrahedron 1962, 17, 79-87.
(
(
4) Deady, L. W.; Quazi, N. H. Aust. J . Chem. 1992, 45, 2083-2087
5) Puchala, A.; Belaj, F.; Bergman, S.; Kappe, C. O. J . Heterocycl.
Chem. 2001, 38, 1345-1352.
(
(
6) Brimert, T. Ph.D. Thesis, KTH, Stockholm, 1998, pp 40-41.
7) Bergman, J .; Bergman, S.; Brimert, T. Tetrahedron 1999, 55,
1
0447-10466.
8) Latypov, N. V.; Bergman, J .; Langlet, A.; Wellmar, U.; Bemm,
U. Tetrahedron 1998, 54, 11525-11536.
9) Bergman, J .; Bergman, S. Tetrahedron Lett. 1996, 37, 9263-
266.
10) Langlet, A.; Latypov, N. V.; Wellmar, U.; Goede, P.; Bergman.
J . Tetrahedron Lett. 2000, 41, 2011-2013.
(
(
(11) Schofield, K. Aromatic Nitration; Cambridge University
Press: Cambridge, 1980; pp 346-360
(12) Organic Synthesis; J ohn Wiley and Sons: New York, 1943;
Collect. Vol. II, pp 440-441
9
(
1
0.1021/jo025952x CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/11/2002
J . Org. Chem. 2002, 67, 7833-7838
7833

Langlet et al.
SCHEME 1
SCHEME 2
conversion to the corresponding dinitro derivative was
observed after 2 h at ambient temperature. When the
reaction medium was changed from sulfuric acid to oleum
the rate of nitration decreased dramatically: nitration
of 2b in 101-105% sulfuric acid gave no gem-dinitro
products after several days at the same reaction condi-
a vigorous reaction accompanied by evolution of carbon
dioxide and precipitation of 4a . This particular finding,
summarized in Scheme 1, and compounds 3a ,c and 4a ,c
were first presented by us in J une 2000.15 Half of a year
later Boyle et al. described an analogous nitration of
2-amino-4,6-(3H,5H)-pyrimidinedione (1a ) and 2-amino-
tions. This is reminiscent of the observations made by
Golod et al. while studying the nitration of nitroform.13
6
-chloro-4(3H)-pyrimidinone, as well as compound 4a ,
At higher concentrations (>5%) of the substrates 1b,c
in sulfuric acid the gem-dinitro products 3b,c crystallized
from the reaction media during the nitration. Both
products reacted vigorously with water, forming deriva-
tives of gem-dinitroacetylurea (4b,c), thus precluding
aqueous workup of the reaction mixtures. Isolation of
1
6
without mentioning our original work. Instead of mixed
acids these authors used solutions of potassium nitrate
in sulfuric acid, claiming that the latter system ensured
a more easily controlled course of nitration and higher
yields of gem-dinitrated products. Contrary to their
observations we found that the use of mixed acids gave
3
b,c in pure form could only be achieved by repeated
essentially the same results as the KNO
is not too surprising since it is well-known that small
amounts of both HNO and KNO are converted quan-
3
solutions. This
washing with trifluoroacetic acid (TFA) to remove all
traces of sulfuric acid. Both compounds proved to be
rather thermally stable (∼150 °C dec) and their struc-
tures as 5,5-gem-dinitro derivatives were confirmed by
NMR studies and elemental analyses.
3
3
titatively in concentrated sulfuric acid to nitronium
ions.17
Isolation of 3b,c in pure form made it possible to study
the properties and reactions of this type of compounds
in more detail with 3b as a typical representative. The
presence of the strongly electronegative gem-dinitro
group in the molecule rendered the adjacent carbonyl
carbon atoms extremely susceptible to various nucleo-
philes, which was demonstrated by the easy hydrolytic
ring cleavage during aqueous workup of the reaction
mixtures (vide supra).
The nature of the products formed in these reactions
was dependent on the reaction conditions used and the
character of the nucleophile.
Compounds 3b,c were demonstrated to dissolve readily
in cold water forming acidic solutions, from which on
standing carbon dioxide evolved resulting in the precipi-
tation of gem-dinitroacetylureas 4b and 4c. These com-
pounds are strong acids forming rather insoluble salts
on careful neutralization of their aqueous solutions (5b,c)
Dinitration of barbituric acid by nitrogen pentoxide
in organic solvents had a long time ago been claimed
by Runge,14 who assigned the structure of the product
as 1,5-dinitrobarbituric acid in analogy with other N-
nitrated aliphatic amides in the series. Their assignment
was exclusively based on the elemental analysis of
the product in the form of a 1:1 complex with dioxane,
despite the fact that the calculated figures for the
suggested structure did not coincide with the experi-
mental data; instead, the reported elemental analysis
gives an excellent correlation with a 1:1 complex of gem-
dinitroacetylurea (4b)and dioxane. Furthermore, in our
hands, the described synthetic procedure gave exclusively
a mixture of 5-nitro and 5,5-gem-dinitro barbituric acid.
All these data imply that the authors were dealing with,
in fact, gem-dinitrated barbituric acid. We were unable
to isolate 2-amino-5,5-dinitropyrimidine-4,6-dione (3a )
from the reaction media even at a very high substrate
(Scheme 2). Treating 5b,c with potassium hydroxide
(
2a ) concentration (>20%), presumably due to the forma-
under more vigorous reaction conditions led to the
formation of potassium dinitromethanide (6) in high
yield.
Weak nucleophiles such as alcohols react smoothly
with 3b at ambient temperature forming derivatives of
the urethane (9), thus confirming that the reaction site
for the initial nucleophilic attack is the 4(6)-carbonyl
tion of a soluble salt as a result of protonation of the
exocyclic amino function in the molecule. Neither did
addition of TFA to the mixture help to induce its
crystallization.
Formation of this product was postulated on the basis
of the following results: the ensuing aqueous workup of
the reaction mixtures produced by nitration of 1a re-
sulted, as in the case with solutions containing 3b,c, in
(15) Latypov, V. N.; Langlet, A.; Wellmar, U.; Goede, P. 31st
International Annual Conference of ICT.
(
13) Mints, E. S.; Golod, E. L.; Bagal, L. I. J . Org. Chem. USSR
(16) Boyle, P. H.; Daly, K. M.; Leurquin, F.; Robinson, J . K.; Scully.
D. T. Tetrahedron Lett. 2001, 42, 1793-1795
(17) Reference 11, pp 97-98.
1
969, 5.
(14) Runge, J .; Treibs, W. J . Prakt. Chem. 1962, 4, 223-227.
7
834 J . Org. Chem., Vol. 67, No. 22, 2002

5
,5-gem-Dinitropyrimidine-4,6-diones
SCHEME 3
SCHEME 4
which easily forms suitable crystals, was investigated by
single-crystal X-ray diffraction methods.
The unit cell consists of two molecules, a and b, with
slightly different out of plane angles of one of the two
nitro groups present in each molecule as can be seen in
Figure 1. The entire unit cell, both a and b, is planar
and only one of the gem-dinitro groups in each molecule
is out of the plane. In molecule a this nitro group is
bent downward and in molecule b it is bent upward
(Figure 1). The geometries of the nitro groups are as
expected, having one shorter and one longer nitrogen-
oxygen bond, with bond distances varying between
1
.23(1) and 1.26(1) Å.
The following bond distances are obtained for the
nitrogen, oxygen, and carbon atoms in the main chain of
the two molecules excluding the nitro group oxygen
atoms: N(4a)-C(3a)-O(4a)- -N(3a)-C(2a)-O(2a)- -C(1a)-
N(1a)- -N(2a) 1.30, 1.23, 1.41, 1.38, 1.23, 1.48, 1.39, and
carbon. Thiols proved to be too weak nucleophiles and
did not react with 3b, instead ring opening with water
was observed. Certain nucleophiles such as amines and
ammonia reacted violently with 3b and formed rather
complex mixtures of products, so that low temperature
and high dilution of reagents had to be used to achieve a
controlled course of the reaction. Under these conditions
pure products of the type 10 and 12 were isolated in
relatively high yields. The results are summarized in
Scheme 3.
It was found that these compounds were also liable to
nucleophilic attacks, though in this case more vigorous
reaction conditions were necessary (Scheme 3). In most
cases the reaction site was again the carbonyl carbon
adjacent to the gem-dinitro group with the latter acting
as a leaving group. The reaction products varied depend-
ing on the nature of the nucleophile used: reactions with
amines lead to formation of symmetrical (8) or unsym-
metrical triureas (7) and probably salts of dinitromethane
1
.41 Å with esd’s of 0.01 Å and N(4b)-C(3b)-O(4b)- -N(3b)-
C(2b)-O(2b)- -C(1b)-N(1b)- -N(2b) 1.34, 1.23, 1.40, 1.37,
.23, 1.46, 1.40, and 1.41 Å with esd’s of 0.01 Å,
1
respectively. The bond angles around the carbon atoms
C(1)-C(3) all lie in the interval of 117-122°. The bond
distances and angles for the two molecules a and b
2
clearly indicate sp -hybridization of the carbon. The
planar geometry of the gem-dinitroacetylurea ion is
stabilized by strong intramolecular hydrogen bonding.
Two of the three hydrogen atoms in each molecule are
participating in strong intramolecular hydrogen bonding
with the following donor-acceptor distances O(21a)-
N(3a) 2.64(1) Å, N(4a)-O(2a) 2.67(1) Å, O(21b)-N(3b)
2
.67(1) Å, N(4b)-O(2b) 2.67(1) Å. The two hydrogen
bonds are both part of a six-membered intramolecular
ring conformation, stabilizing the planar configuration.
Additional evidence for the presence of hydrogen
bonding in the molecule came from the analyses of the
(as was indicated by UV spectroscopy of the mother
liquor). There was only one example of a nucleophilic
attack at the urea carbon. In the reaction of 12 with
morpholine 13 was formed; however, the reaction of 9
with ethanol gave 11.
1
H NMR spectrum of the potassium salt of 4b. Normally
1
one would expect two peaks in the H NMR spectrum,
instead three peaks were observed at room temperature
corresponding to the NH and NH
believe that one of the hydrogen atoms in the NH
is participating in hydrogen bonding thus leading to
splitting of the NH peak. To verify this hypothesis
dynamic H NMR experiments were performed on the
2
groups. This made us
Similar reactions of 5,5-disubstituted barbituric acids
were observed by Ziegler and Kappe while investigating
the properties of 5-chloro-5-nitrobarbituric acid (14). Thus
treating 14 with water led to evolution of carbon dioxide
and precipitation of chloronitroacetyl urea (15).18 Reac-
tion with other nucleophiles also resembles the behavior
of 3b, where the treatment of 14 with morpholine led
to isolation of the morpholinium salt of 1-(2-chloro-2-
nitroacetyl)-3-(morpholino-4-carbonyl)urea (16). It was of
interest to elucidate the structural configuration of the
rather unusual group of dinitroacetylureas 4a -c. As an
example, the potassium salt of 2,2-dinitroacetylurea (5b),
2
group
2
1
6
salt with DMSO-d as solvent.
Variable-temperature 1H NMR measurements were
performed in the range from +25 to +75 °C. At each
temperature the sample was stabilized for a minimum
of 10 min.
A relatively high coalescence temperature (65 °C)
was observed for substance 6b when the NH-doublet at
7
1
.5 ppm merged into a singlet at 7.0 ppm and a ∆ν )
45 Hz was observed at room temperature (298 K)
(18) Ziegler, E.; Kappe, Th. Monatshefte 1964, 95, 1057-1060
(Figure 2). From these figures the activation energy for
J . Org. Chem, Vol. 67, No. 22, 2002 7835

Langlet et al.
F IGURE 1. The molecular conformation and atom labeling of the gem-dinitroacetylurea ion. Molecule a on the left and b on the
right. The lower figure illustrates the planar geometry of the molecule and the different angle of one of the two nitro groups.
from the anion of dinitromethane (6)16,19 produced by
partial hydrolysis of the substance.
Su m m a r y a n d Con clu sion s
gem-Dinitration in the heterocyclic ring of the pyrimi-
dinone series (barbituric acid, 1,3-dimethylbarbituric
acid, and 2-amino-4,6-dihydroxypyrimidine) was discov-
ered. The gem-dinitro compounds formed were easily
hydrolyzed to derivatives of gem-dinitroacetylurea and
gem-dinitroacetylguanidine, which could be further hy-
drolyzed to dinitromethane salts. Ring opening of gem-
dinitro pyrimidinones with nucleophiles gave new gem-
dinitroacetyl derivatives, while more forcing conditions
and strong nucleophiles gave symmetric or asymmetric
triurea compounds as well as salts of dinitromethane.
Hydrolysis of 5,5-dinitrobarbituric acid provides a new,
efficient, and safe method for the preparation of dinitro-
2
0-22
methane in comparison with other known methods.
1
F IGURE 2. Partial variable-temperature 300-MHz H NMR
Exp er im en ta l Section
6
spectra recorded in DMSO-d .
NMR spectra were obtained on a Bruker Avance 400 or a
J EOL Eclipse+ 500. Infrared spectra were recorded with a
Perkin-Elmer 1600 FTIR. Melting points and decomposition
temperatures were recorded with a Mettler DSC 30. Elemental
analyses were carried out by H Kolbe Mikroanalytisches
Laboratorium, M u¨ lheim an der Ruhr, Germany.
q
rotation (∆G ) was calculated according to the Eyring
equation:25
q
∆
G
) 4.58T (10.32 + log T / k ) cal/mol
Tc c c c
(
19) Fedorov, Y. A.; Odokienko, S. S.; Selivanov, V. F. J . Appl. Chem.
q
where k
c
) π∆ν/x2 and T
c
) 338 K. ∆G was found to be
USSR 1979, 52, 2201-2202.
equal to 16.0 kcal/mol, thus indicating the existence of
strong hydrogen bonding and hindered rotation around
C(3) and N(4). At elevated temperatures an additional
peak at ca. 8.1 ppm appears, which probably originates
(20) Grakauskas, V.; Guest, A. M. J . Org. Chem. 1978, 43, 3485-
3
488 and references therein.
(
21) Grakauskas, V. U.S. patent 4.233.250, 1979.
(22) Garver, L. C.; Grakauskas, V.; Baum, K. J . Org. Chem. 1985,
50, 1699-1702.
7
836 J . Org. Chem., Vol. 67, No. 22, 2002

5
,5-gem-Dinitropyrimidine-4,6-diones
Ca u tion : The gem-dinitrocompounds described in this
g, 0.001 mol) was added to a solution of potassium carbonate
(0.002 mol) in water (30 mL) and a pale yellow precipitate was
paper are powerful and sensitive explosives and should be
handled with appropriate precautions. Employ all standard
energetic materials safety procedures in experiments involving
such substances. Crystallographic data (excluding structure
factors) for the structure in this paper have been deposited
with the Cambridge Crystallographic Data Centre as supple-
mentary publication number CCDC 143142. Copies of the data
can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK. (fax: +44(0)-1223-
formed (0.19 g, 0.75 mmol, 75%). IR (KBr) 3428, 3024, 1687
1
(CdO), 1574 (C(NO
2
)
2
), 1334 (C(NO
2
)
2
); H NMR (DMSO-d
6
)
δ 8.73 (q, 1H, J ) 4.02), 3.38 (s, 3H), 2.76 (d, 3H, 4.02); 3C
NMR (DMSO-d ) δ 165.06, 155.67, 131.77, 31.73, 27.75; 190
°C dec, Anal. Calcd for C K: C, 23.26; H, 2.73; N, 21.70.
1
6
5
6 4 6
H N O
Found: C, 23.37; H, 2.80; N, 21.64.
P ota ssiu m Din itr om eth a n e (6). Potassium gem-dinitro-
acetylurea (5b) (10 g, 0.052 mol) was added to the solution of
KOH (12 g, 0.21 mol) in water (100 mL); the resulting mixture
was kept at 80 °C for 2 h and then cooled to room temperature.
The precipitate of potassium dinitromethane was filtered,
washed with 10-15 mL of cold water, and dried to give 6.2 g
(0.044 mol, 85%) of pure potassium dinitromethane (6), which
3
36033 or e-mail: deposit@ccdc.cam.ac.uk).
,5-Din itr oba r bitu r ic Acid (3b). To a mixture of barbi-
turic acid (1b) (12.8 g, 0.1 mol) dissolved in 95% sulfuric acid
60 mL) was added fuming nitric acid (10 mL, 0.24 mol) while
5
(
the temperature was kept below 25 °C. The reaction mixture
was then heated to 45 °C for 4 h. The resulting precipitate
was filtered, washed with TFA, and dried, yielding 5,5-
dinitrobarbituric acid (3b) as a hemihydrate (21.3 g, 0.094 mol,
2
0
was identified by its decomposition temperature of 220 °C
1
6,19
and UV spectroscopy (λmax ) 363 nm and ꢀ ) 20 800);
1
13
H NMR (DMSO-d
6
) δ 8.16; C NMR (DMSO-d
6
) δ 123.66.
9
4%), 150 °C dec; IR (KBr) 3252(NH), 1745 (CdO), 1611 (Cd
gem -Din itr oa cetylgu a n id in (4a ). 2-Aminopyrimidine-4,6-
1
O), 1580 C(NO
2
)
2
, 1378 C(NO
br; C NMR (DMSO-d ) δ 113.5, 149.0, 155.1. Anal. Calcd for
O: C, 21.16; H, 1.33; N, 24.67. Found: C, 21.11;
H, 1.23; N, 24.89.
,3-Dim eth yl-5,5-d in itr op yr im id in e-2,4,6-tr ion e (3c).
2
)
2
; H NMR (DMSO-d
6
) δ 11.03
dione (1a ) (3.8 g, 0.018 mol) dissolved in concentrated sulfuric
acid (40 mL) was nitrated under conditions analogous to those
for 3b. After 2 h the reaction mixture was cooled to room
temperature and poured into cold water (200 mL); the dilution
was accompanied by evolution of carbon dioxide and precipita-
tion of a yellow solid, 4a (5.0 g, 0.016 mol, 88%); 150 °C dec;
1
3
6
1
C
4
H
2
N
4
O
7
2 2
‚ / H
1
N,N′-Dimethyldinitrobarbituric acid (1c) (3.9 g, 0.025 mol) was
added to sulfuric acid (78 mL, 95%), and nitric acid (2.3 mL,
0
temperature was raised to 40 °C for 4.5 h. A white precipitate
was formed after 30 min. After standing at ambient temper-
ature for 3 h the precipitate was collected and washed with
TFA, yielding 1,3-dimethyl-5,5-dinitropyrimidine-2,4,6-trione
IR (KBr) 3412 (CONH
(C(NO ), 1371 (C(NO
1H), 8.8 (br s, 2H), 8.11 (br s, 2H); C NMR (DMSO-d
157.55, 155.75, 135.34. Anal. Calcd for C : C, 18.85;
2
), 1685 (CONH
2
), 1672 (CONH
); H NMR (DMSO-d ) δ 11.4 (br s,
) δ
2
), 1572
1
.055 mol) was added dropwise at 30 °C during 30 min. The
2
)
2
2
)
2
6
1
3
6
3
5 5 5
H N O
H, 2.62; N, 36.65. Found: C, 19.01; H, 2.60; N, 36.57.
Am m on iu m Sa lt of (2,2-Din itr oa cetyl)biu r et (10) a n d
Ur eoid oca r bon ylu r ea (8). 5,5-Dinitrobarbituric acid (3b) (2
g, 0.009 mol) was added to ammonia (40 mL, 25%) at 5-10
°C. A yellow precipitate was formed. A sample was collected
and dried, yielding yellow crystals of the ammonium salt of
(3c) (4.8 g, 0.0195 mol, 78%); IR (KBr) 1715 (CdO), 1597
1
13
C(NO
2
)
2
, 1366 C(NO
) δ 154.14, 149.13, 107.73, 31.10; mp 178 °C. Anal.
Calcd for C : C, 29.28; H, 2.46; N, 22.76. Found: C,
9.38; H, 2.51; N, 22.59.
gem -Din itr oa cetylu r ea (4b). Dinitrobarbituric acid (3b)
7.2 g, 0.032 mol) was dissolved at 10 °C in water (10 mL) and
2 2 6
) ; H NMR (DMSO-d ) δ 3.28; C NMR
(DMSO-d
6
6
6 4 7
H N O
2
(2,2-dinitroacetyl)biuret (10) as a dihydrate; 94 °C dec; IR
+
(KBr) 3447 (NH
4
), 1742 (CONH
) δ 11.04 (s, 1H), 10.06 (s, 1H),
7.35 (s, 2H), 7. 7 (s, 4H); C NMR (DMSO-d ) δ 158.88, 153.79,
152.37, 134.54. Anal. Calcd for C ‚2H O: C, 16.67; H,
2 2 2
), 1510 (C(NO ) ), 1395
1
(
2 2 6
(C(NO ) ); H NMR (DMSO-d
1
3
kept at this temperature for 2 h; during this period gas
evolution was observed, which resulted in the precipitation of
a yellow solid. The solid was filtered and dried at 40 °C with
a color change from yellow to white to give 4b (5.5 g, 0.017
6
4
H
8
N
6
O
7
2
4.16; N, 29.16. Found: C, 16.37; H, 4.16; N, 29.16. The reaction
mixture was refluxed for 20 min and a white precipitate was
formed. The precipitate was collected, washed with ethanol,
and dried, yielding ureoidocarbonylurea (8) (0.32 g, 0.002 mol,
24%). Elemental analysis and spectroscopic data were in all
mol, 53%); 130 °C dec; IR (KBr) 3501 (CONH
780 (CONH ), 1719 (CONH ), 1595 (C(NO
NO
H). Anal. Calcd for C
2
), 3045 (CONH
2 2
), 1356 (C(NO )
2
),
);
1
2
2
2
)
2
1
H NMR (CD
3
2
) δ 9.4 (br s, 1H), 7.64 (br s, 1H), 5.94 ( br s,
2
3
1
3
H
4
N
4
O
6
: C, 18.75; H 2.08; N, 29.17.
respects identical with data given in the literature.
Found: C, 18.78; H, 2.26; N, 29.14. It was not possible to obtain
a carbon-13 NMR of gem-dinitroacetylurea (4b) due to low
stability in solution.
P ot a ssiu m gem -Din it r oa cet ylu r ea (5b ). gem-Dinitro-
acetylurea (4b) (10 g, 0.052 mol) dissolved in water (50 mL)
was added dropwise to a solution of KOH (2.7 g, 0.05mol) in
Mor p h olin e Sa lt of 1-(2,2-Din itr oa cetyl)-3-(m or p h o-
lin e-4-ca r bon yl)u r ea Com p lexed w ith 1 equ iv of Mor -
p h olin e (12). 5,5-Dinitrobarbituric acid (3b) (1 g, 0.0045 mol)
was added to morpholine (30 mL) at 0-10 °C. After addition
the reaction mixture was heated to 30 °C for 10 min. Cooled
diisopropyl ether (30 mL) was added and a white precipitate
was formed. The precipitate was collected, washed with
ethanol, and dried, yielding the morpholine salt of 1-(2,2-
Dinitroacetyl)-3-(morpholine-4-carbonyl)urea (12) as a complex
5
0 mL of water while keeping the temperature at 10 °C. A
yellow precipitate was immediately formed, which was filtered
and dried. Yield 8.2 g (0.027 mol, 77%) of potassium gem-
with one molecule of morpholine (2.1 g, 0.0043 mol, 97%); 150
dinitroacetylurea (5b); 160 °C dec; IR (KBr) 3418 (CONH
2
),
),
C
+
°
C dec; IR (KBr) 3412 (R
2
NH
2
), 1737 (CdO), 1524 (C(NO
2
)
2
),
3
1
335 (CONH
2
), 1728 (CONH
2
), 1635 (CONH
); H NMR (DMSO-d ) δ 10.44, 7.66, 7.21;
) δ 159.15, 154.90, 134.99. Anal. Calcd for
K: C, 15.65; H, 1.31; N, 24.34. Found: C, 15.46; H,
2 2 2
), 1580 (C(NO )
1
1
13
1398 (C(NO ) ); H NMR (DMSO-d ) δ 7.29 (br s, 4H, NH),
398 (C(NO
2
)
2
6
2
2
6
3
3
.65 (t, 8H, CH
2
, J ) 5.0 Hz), 3.58 (t, 4H, CH , J ) 5.0 Hz),
2
NMR (DMSO-d
6
13
.40 (t, 4H, J ) 5.0 Hz) 2.93 (t, 8H, CH , J ) 5.0 Hz); C NMR
2
C
3
H
3
N
4
O
6
(DMSO-d
6
) δ 157.53, 151.82, 149.46, 133.92, 65.72, 64.80,
1
.28; N, 24.22.
4
4.09. Anal. Calcd for C16 10: C, 40.08; H, 6.05; N, 20.45.
29 5
H N O
On e-P ot P r ep a r a tion of P ota ssiu m Sa lt of (2,2-Din itr o-
Found: C, 39.64; H, 6.08; N, 20.30.
-(2,2-Din itr oa cetyl)-3-(ca r bon yl eth yl ester )u r ea (9).
,5-Dinitrobarbituric acid (3b) (2 g, 0.011 mol) was added to
a cetyl)u r ea (4b) fr om gem -Din itr oba r bitu r ic Acid (3b).
,5-Dinitrobarbituric acid (3b) (5 g, 0.022 mol) was added to
water (10 mL) at 10 °C and a solution of potassium hydroxide
1.3 g, 0.023 mol) in water (5 mL) was added. Gas evolution
1
5
5
ethanol (10 mL). The mixture was heated to 79 °C for 30 min
resulting in a yellow solution, which was concentrated to 5
mL; hexane (20 mL) was added to the solution and a yellow
precipitate was formed. The precipitate was collected and
dried, yielding 1-(2,2-dinitroacetyl)-3-(carbonyl ethyl ester)urea
(
was observed. The temperature was raised to 25 °C for 30 min.
A yellow precipitate was formed. The precipitate was collected
and dried to yield the potassium salt of (2,2-dinitroacetyl)urea
(4b) as yellow crystals (3.2 g, 0.014 mol, 63%).
P ota ssiu m Sa lt of N,N-Dim eth yl-gem -d in itr oa cetyl-
u r ea (5c). N,N-Dimethyl-gem-dinitrobarbituric acid (3c) (0.25
(23) Haworth, R. C.; Mann, F. G. J . Chem. Soc. 1943, 603-606.
J . Org. Chem, Vol. 67, No. 22, 2002 7837

Langlet et al.
(
(
(
9) (1.3 g, 0,005 mol, 44%); 120 °C dec; IR (KBr) 3368
CONH R), 1702 (CdO), 1657 (CdO)1575 (C(NO ), 1238
C(NO ) δ 11.41 (s, 1H), 11.64 (s, 1H),
0.30 (br s, 1H), 4.14 (q, 2H, CH , J ) 7.1 Hz), 1.22 (t, 3H,
, J ) 7.1 Hz); C NMR (DMSO-d ) δ 157.48, 155.27,
: C,
7.28; H, 3.05; N, 48.46. Found: C, 27.64; H, 3.15; N, 20.96.
,5-Dinitrobarbituric acid (3b) (4 g, 0.0183mol) was added
1-(Mor p h olin o-4-ca r bon yl)-3-(ca r bon yl eth yl ester )-
u r ea (7). 1-(2,2-Dinitroacetyl)-3-(carbonyl ethyl ester)urea
(9) (2 g, 0.0076 mol) was added to a solution of morpholine
(1.3 mL, 0.015 mol) in dioxane (11 mL). The reaction mixture
was refluxed for 30 min and a pale red precipitate was formed.
Recrystallization from dioxane (20 mL) and drying gave
1-(morpholin-4-carbonyl)-3-(carbonyl ethyl ester)urea (7) (0.5
2
2 2
)
1
2 2 6
) ); H NMR (DMSO-d
1
CH
1
2
2
1
3
3
6
6 8 4 8
49.55, 134.80, 62.72, 14.82. Anal. Calcd for C H N O
5
g, 0.0017 mol, 23%) as white crystals; mp 180 °C; IR (KBr)
1
to ethanol (15 mL) and the mixture was refluxed for 40 min.
The yellow precipitate formed was filtered, washed with
petroleum ether, and dried, yielding 1-(2,2-dinitroacetyl)-3-
3262 (CONH
NMR (DMSO-d
(q, 2H, CH , J ) 7.1 Hz), 3.57 (t, 4H, CH
4H, J ) 4.7 Hz), 1.21 (t, 3H, CH , J ) 7.1 Hz); C NMR
(DMSO-d ) δ 153.17, 151.52, 149.36, 65.66, 61.38, 44.15, 14.08.
Anal. Calcd for C C, 44.08; H, 6.17; N, 17.13.
2
R), 1800 (CO
2
R), 1694 (CdO), 1657 (CdO); H
6
) δ 10.96 (s, 1H, NH), 9.78 (s, 1H, NH), 4.12
2
2
, J ) 4.7 Hz), 3.41 (t,
1
3
(carbonyl ethyl ester)urea (9) (4.12 g, 0.0156 mol, 85%).
3
Eth yl(a m in oca r bon yl)ca r ba m a t fr om 5,5-Din itr oba r -
6
bitu r ic Acid (11). 5,5-Dinitrobarbituric acid (3b) (2 g, 0.011
mol) was added to ethanol (15 mL) at ambient temperature.
After 48 h a white precipitate was collected and characterized
as ethyl(aminocarbonyl)carbamate.24
Mor p h olin e Sa lt of 1-(2-Ch lor o-2-n itr oa cetyl)-3-(m or -
p h olin o-4-ca r bon yl)u r ea (16). 5-Chloro-5-nitrobarbituric
acid (14) (2 g, 0.0097 mol) was added to morpholine with
cooling. The reaction mixture was refluxed for 15 min, yielding
pale red precipitate; dioxane was added (10 mL) and the
precipitate was collected. Recrystalization from dioxane (40
mL) gave 1-(2-chloro-2-nitroacetyl)-3-(morpholine-4-carbonyl)-
9 15 3 5
H N O :
Found: C, 44.15; H, 5.80; N, 17.15.
Bis(m or p h olin o-4-ca r bon yl)a m id e (13). 5,5-Dinitrobar-
bituric acid (3 g, 0.0135 mol) was added to morpholin (16.5
mL) at 0-10 °C. The reaction mixture was heated to reflux
for 1 h. On cooling an orange precipitate was formed. The
precipitate was collected and washed with n-heptane and
dioxane; recrystallization from dioxane (40 mL) gave bis-
(morpholin-4-carbonyl)amide (13) (1 g, 0.0046 mol, 34%) as
2
white needles; mp 180 °C; IR (KBr) 2975 (CH ), 1685 (CdO),
1
1651 (CdO) 1248 (CdO); H NMR (DMSO-d ) δ 8.60 (s, 1H,
6
urea (16) as a morpholine salt (2.1 g, 0.0055 mol, 57%); 170
NH), 3.54 (t, 8H, CH , J ) 5.0 Hz), 3.32 (t, 8H, CH , J ) 5.0
2
2
+
13
°
C dec; IR (KBr) 3062 (R
2
NH
2
), 1742 (CdO
2
), 1636 (CdO);
Hz); C NMR (DMSO-d ) δ 154.19, 66.91, 44.56. Anal. Calcd
6
1
H NMR (DMSO-d
6
) δ 12.51 (s, 1H, NH), 11.11 (s, 1H, NH),
), 3.75 (t, 4H, CH , J ) 5.0 Hz), 3.60 (t, 4H,
, J ) 5.0 Hz), 3.38 (t, 4H, CH , J ) 5.0 Hz), 3.10 (t, 4H,
, J ) 5.0 Hz); C NMR (DMSO-d ) δ 160.27, 150.87,
for C H N O : C, 49.37; H, 7.04; N, 17.27. Found: C, 49.10;
1
0
17
3
3
8
CH
CH
.62 (br s, 2H, NH
2
2
H, 7.81; N, 17.18.
2
2
2
1
3
6
1
49.38, 108.85, 65.73, 65.37, 42.98. Anal. Calcd for C12
ClN : C, 37.75; H, 5.28; N, 18.34. Found: C, 37.45; H, 5.25;
N, 17.54.
20
H -
Ack n ow led gm en t. The authors would like to thank
the Swedish Defence Forces for giving financial support
to this project
5
O
7
(
(
24) Bussas, R.; Kresze, G. Liebigs Ann. Chem. 1982, 3, 545-563.
25) See for example: G u¨ nther, H. NMR Spectroscopy, 2nd ed.;
Wiley: Chichester, 1995; pp 343-4.
J O025952X
7
838 J . Org. Chem., Vol. 67, No. 22, 2002